Prevention of Infection in Patients With Hematologic Cancer and Persistent Fever Caused by a Low White Blood Cell Count

Condition(s) targeted: Bone Marrow Suppression; Fever, Sweats, and Hot Flashes; Infection; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Intervention: piperacillin sodium (Drug); piperacillin-tazobactam (Drug); tazobactam sodium (Drug); vancomycin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: European Organisation for Research and Treatment of Cancer - EORTC

Official(s) and/or principal investigator(s):
Michel P. Glauser, MD, Study Chair, Affiliation: Centre Hospitalier Universitaire Vaudois

RATIONALE: Antibiotic therapy may prevent the development of infection in patients with hematologic cancer and the persistent fever caused by a low white blood cell count. It is not yet known which regimen of antibiotics is most effective in preventing infection in these patients. PURPOSE: Randomized phase III trial to study the effectiveness of piperacillin-tazobactam with or without vancomycin in reducing fever in patients who have leukemia, lymphoma, or Hodgkin's disease.

Official title: Vancomycin Versus Placebo in Persistently Febrile Granulocytopenic Patients Given Piperacillin/Tazobactam

Study design: Allocation: Randomized, Primary Purpose: Supportive Care

Detailed description: OBJECTIVES: I. Compare the efficacy of piperacillin and tazobactam with or without vancomycin in reducing fever in patients with hematological malignancies and persistent febrile granulocytopenia. OUTLINE: This is a randomized, double blind, multicenter study. Patients receive piperacillin/tazobactam IV over 20-30 minutes every 6 hours. Patients who become afebrile within 48-60 hours after beginning treatment continue to receive piperacillin/tazobactam alone. These afebrile patients continue treatment for a minimum of 7 days, of which 4 must be consecutive without fever. Patients who are still febrile after the initial 48-60 hours are randomized to continue on piperacillin/tazobactam alone or with vancomycin. Vancomycin IV is administered over at least 1 hour twice daily. Treatment continues for a maximum of 28 days in the absence of persistent fever. Patients are followed at 7-10 days after completion of therapy. PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study.

Minimum age: 2 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Leukemia, lymphoma, or Hodgkin's disease OR Stem cell transplantation or bone marrow transplantation (allogenic or autologous) for a neoplastic disease Absolute granulocyte count no greater than 1,000/mm3 anticipated to fall below 500/mm3 within 24-48 hours, and expected to last for longer than 7 days from onset of fever Fever (i. e., oral or axillary temperature at least 38. 5 degrees C or 101. 3 degrees F once, or at least 38 degrees C or 100. 4 degrees F on two or more occasions separated at least by 1 hour during a 12 hour period) Presumed infection PATIENT CHARACTERISTICS: Age: 2 and over Performance status: Not moribund or comatose for any reason with little hope of recovery Life expectancy: At least 48 hours Hematopoietic: See Disease Characteristics Hepatic: No hepatic stupor or coma Renal: Adults: No renal failure requiring hemodialysis or peritoneal dialysis OR Creatinine no greater than 2. 25 mg/dL OR Creatinine clearance at least 40 mL/min Children: No renal impairment (i. e., creatinine greater than upper limit of normal) Pulmonary: No lung infiltrate Other: No known allergy to piperacillin, tazobactam, or vancomycin No history of immediate or accelerated reaction to beta-lactam antibiotics No prior inclusion in this study No catheter related infection No known HIV infection Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: At least 4 days since prior intravenous antibacterial agents Oral antibiotics for prophylaxis of bacterial infection allowed At least 30 days since prior treatment with any other investigational antibiotic No other concurrent antibiotics except trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia

Algemeen Ziekenhuis Middelheim, Antwerp 2020, Belgium

Cliniques Universitaires Saint-Luc, Brussels (Bruxelles) 1200, Belgium

Institut Jules Bordet, Brussels (Bruxelles) 1000, Belgium

Hopital Universitaire Erasme, Brussels 1070, Belgium

Masaryk University Hospital, Brno 639 00, Czech Republic

Turku University Central Hospital, Turku FIN-2-0521, Finland

CHR de Besancon - Hopital Saint-Jacques, Besancon 25030, France

Klinikum der Universitaet Ulm, Ulm D-89081, Germany

Athens University-Laikon General Hospital, Athens 11527, Greece

Hellenic Institute for Cancer-Saint Savas Hospital, Athens 11522, Greece

Metaxa's Memorial Cancer Hospital, Piraeus 18537, Greece

University of Patras Medical School, Rio Patras GR-26500, Greece

Wolfson Medical Center, Holon 58100, Israel

Hadassah University Hospital, Jerusalem 91120, Israel

Chaim Sheba Medical Center, Ramat-Gan 52621, Israel

National Cancer Institute - Bratislava, Bratislava 833 10, Slovakia

St. Elizabeth Cancer Institute Hospital, Bratislava SK-81250, Slovakia

Ospedale San Giovanni, Bellinzona CH-6500, Switzerland

Centre Hospitalier Universitaire Vaudois, Lausanne CH-1011, Switzerland

Universitaetsspital, Zurich CH-8091, Switzerland

Ibn-i Sina Hospital, Ankara Univeristy, Ankara 06100, Turkey

Section of Infectious Diseases, Ankara 06100, Turkey

Marmara University Hospital, Istanbul 81190, Turkey

Royal Marsden Hospital, Sutton, England SM2 5PT, United Kingdom

Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201, United States

Boston Medical Center, Boston, Massachusetts 02118, United States

Kingston General Hospital, Kingston, Ontario K7L 2V7, Canada

Ottawa Regional Cancer Center - General Division, Ottawa, Ontario K1H 8L6, Canada

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: November 1997
Last updated: September 20, 2012